The NIDDK Inflammatory Bowel Disease Genetics Consortium
(IBDGC) was established in July, 2002 for the purpose of identifying genes
predisposing to IBD. Since its establishment, the IBDGC, in collaboration
with other international IBD genetics consortia, has identified more than 100
such susceptibility loci. However, many susceptibility genes still remain to
be identified, and the work of elucidating how IBD risk-associated genetic
variants influence the pathophysiology of IBD has barely begun. The purpose
of this FOA is to renew the IBDGC to continue the discovery of susceptibility
variants, and to integrate genomic with epigenomic, transcriptomic,
proteomic, metabolomic, and other -omic methodologies to elucidate the
effects of genetic risk variants on the pathophysiology of IBD. The GRCs
will serve as sites of enrollment of IBD patients, relatives, and healthy
controls for these studies, and for laboratory-based studies on biological
samples taken from these subjects. The PD(s)/PI(s) of the GRCs will serve as
members of the Steering Committee of the IBDGC, which will be responsible for
all of the IBDGC's operational decisions, which will be binding upon all of
the IBDGC's members.

Key Dates

Posted Date

February 9, 2012

Open Date (Earliest Submission Date)

March 30, 2012

Letter of Intent Due Date

March 30, 2012

Application Due Date(s)

April 30, 2012, by 5:00 PM local time of applicant
organization.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

May-June, 2012

Advisory Council Review

October, 2012

Earliest Start Date(s)

December, 2012

Expiration Date

May 1, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in
the SF
424 (R&R) Application Guide, except where instructed to do otherwise
(in this FOA or in a Notice from the NIH Guide for Grants and
Contracts). Conformance to all requirements (both in the
Application Guide and the FOA) is required and strictly enforced. Applicants
must read and follow all application instructions in the Application Guide as
well as any program-specific instructions noted in Section IV. When the program-specific
instructions deviate from those in the Application Guide, follow the
program-specific instructions. Applications that do not comply with
these instructions may be delayed or not accepted for review.

NOD2,
the first IBD susceptibility gene to be identified, was identified by genetic
linkage analysis, followed by association analysis of the genes under the
linkage peak. Most of the remaining susceptibility loci have been identified
by genome-wide association studies (GWAS). The earliest GWAS relied on tagging
regions of linkage disequilibrium using relatively common genetic variants. As
the increasing speed and capacity and decreasing cost of DNA sequencing have
led to the discovery of an increasing number of genetic variants, more recent
GWAS have made use of less common variants, resulting in the identification of
a steadily increasing number of IBD susceptibility loci. While whole-exome and
whole-genome sequencing approaches are coming into increasing use for
identification of very rare variants in Mendelian diseases, methods for the use
of these approaches in the analysis of genetically complex disorders (such as
IBD) are still under development, and the role of rare variants in the genetic etiology
of such disorders is under active investigation. Regardless of what proportion
of the overall heritability of IBD is accounted for by rare variants, such
variants, by virtue of their large effects on disease phenotypes and protein
function or gene expression, can ultimately yield important insights into
pathophysiological mechanisms. The IBDGC, which has already begun to explore
the role of less common variants in IBD, will therefore continue to elucidate
the role of rare variants in IBD, using the most current genotyping,
DNA-sequencing, and statistical analytical methodologies.

The IBDGC will also investigate the mechanisms by which
risk-associated genetic variants influence IBD pathophysiology. Such studies
encompass a wide range of approaches, from genome-wide "-omic" analyses
of the various processes of gene expression and function (e.g., epigenomic,
transcriptomic, proteomic, metabolomic)to highly specialized functional studies of specific gene products
and physiological pathways. The IBDGC will emphasize primarily genome-wide
approaches, though there will be some scope for specialized functional studies,
as budgets permit. In view of the central (but yet to be fully elucidated)
role of the intestinal microbiota in the pathophysiology of IBD, the IBDGC may
also undertake analyses of the composition and activity of the intestinal
microbiome, and integrate the results of these analyses with their genetic
analyses of other IBD-related phenotypes.

The GRCs will recruit subjects into the study, and conduct
phenotypic evaluations of these subjects. They will send blood samples from
newly recruited subjects to a central facility for extraction of DNA. (The
IBDGC may subcontract DNA extraction to a commercial provider of these services.)
The IBDGC may isolate and/or immortalize various types of blood cells from
subjects for functional studies or as a limitless source of DNA. The IBDGC
will send an aliquot of DNA produced from each subject to the NIDDK Biosample Repository
and an aliquot of each cell line produced to the NIDDK Genetics Repository (both
Repositories supported by independent contracts from NIDDK) for eventual
sharing with the broader research community. The GRCs may collect other biological
samples from subjects (e.g.,
stool, intestinal biopsies). The GRCs may carry out genotyping, sequencing,
and other molecular analyses as required by the various projects undertaken.
They will transmit phenotypic, genotypic, and other data to databases
maintained by the Data Coordinating Center (DCC, solicited by the accompanying RFA-DK-11-502).

The goal of the research to be carried out by the IBDGC is
the enhancement of our understanding of the pathophysiologic mechanisms of
IBD. This enhanced understanding will lead to improved methods for diagnosis,
prevention, and treatment of IBD.

This FOA will support the following types of projects, as
well as others not mentioned in this list:

Analyses of the composition and activities of the intestinal
microbiome of recruited subjects.

Analyses of the relationships among host genetic variation,
intestinal microbiome composition and activity, and variation in the presentation,
severity, natural history, and response to treatment of IBD.

The IBDGC has previously achieved some of its most notable
successes in identifying IBD susceptibility loci by collaborating with
international IBD and other disease genetics consortia, pooling data from the
very large numbers of subjects required to detect loci with small effect sizes
in a GWAS. In view of the outstanding success of such collaborations, the
IBDGC is strongly encouraged to maintain and expand them going forward. The
IBDGC is also encouraged to collaborate where appropriate with investigators
who wish to conduct functional studies on IBD risk variants identified by the
IBDGC, but which otherwise lie outside the scope of activities supported by
this FOA.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH
Grants Policy Statement, are allowed.

Required Registrations

Applicant organizations must complete the following registrations
as described in the SF 424 (R&R) Application Guide to be eligible to apply
for or receive an award. Applicants must have a valid Dun and Bradstreet
Universal Numbering System (DUNS) number in order to begin each of the following
registrations.

All Program Directors/Principal Investigators (PD(s)/PI(s))
must also work with their institutional officials to register with the eRA
Commons or ensure their existing eRA Commons account is affiliated with the eRA
Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant
organizations are strongly encouraged to start the registration process at
least 4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal
Investigator(s))

Any individual(s) with the skills, knowledge, and resources
necessary to carry out the proposed research as the Program Director(s)/Principal
Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to
develop an application for support. Individuals from underrepresented racial
and ethnic groups as well as individuals with disabilities are always
encouraged to apply for NIH support.

.Only one application per institution (normally identified
by having a unique DUNS number or NIH IPF number) is allowed.

NIH will not accept any application in response to this FOA
that is essentially the same as one currently pending initial peer review
unless the applicant withdraws the pending application. NIH will not accept any
application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Requesting an
Application Package

Applicants must download the SF424 (R&R) application
package associated with this funding opportunity using the “Apply for Grant
Electronically” button in this FOA or following the directions provided at Grants.gov.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in
the SF424
(R&R) Application Guide, except where instructed in this funding
opportunity announcement to do otherwise. Conformance to the requirements in
the Application Guide is required and strictly enforced. Applications that are
out of compliance with these instructions may be delayed or not accepted for
review.

Although a letter of intent is not required, is not binding,
and does not enter into the review of a subsequent application, the information
that it contains allows IC staff to estimate the potential review workload and
plan the review.

By the date listed in Part 1. Overview
Information, prospective applicants are asked to submit a letter of intent
that includes the following information:

The forms package associated with this FOA includes all
applicable components, mandatory and optional. Please note that some
components marked optional in the application package are required for
submission of applications for this FOA. Follow all instructions in the SF424
(R&R) Application Guide to ensure you complete all appropriate “optional”
components.

Page Limitations

All page limitations described in the SF424 Application
Guide and the Table of
Page Limits must be followed.

SF424(R&R) Senior/Key Person Profile Expanded
Component

As part of the Personal Statement, the Key Person Profile
for the PD(s)/PI(s) should include a description of the individual's previous
experience conducting research as part of a consortium. The description should
include the name of the consortium, a brief (up to 2 sentences) description of
its overall goals, the dates when the research was performed, the individual's
role in the consortium (highlighting any leadership roles, such as committee
chairmanship), the approximate number of PD(s)/PI(s) in the consortium, the
dates, amount, and source of any funding for consortial activities for which
the individual served as PD(s)/PI(s). The Personal Statement should describe
the individual's participation in a maximum of one consortium. If the
individual has no previous research consortium experience, the Personal
Statement should so indicate.

PHS 398 Research Plan Component

All instructions in the SF424 (R&R) Application Guide
must be followed, with the following additional instructions:

Research Strategy

New and renewal applications should distinguish
individual GRC projects from those requiring collaboration with the other GRCs
and DCC.

Progress Report

Renewal applications should distinguish progress on
individual GRC projects from progress on projects carried out in collaboration
with the other GRCs and DCC.

Protection of Human Subjects

The Protection of Human Subjects section should
include a Data and Safety Monitoring Plan.

Resource Sharing Plan

Individuals are required to comply with the
instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model
Organisms, and Genome Wide Association Studies (GWAS) as provided in the SF424
(R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested
for any one year, should address a Data Sharing Plan.

Appendix

Do not use the Appendix to circumvent page limits. Follow
all instructions for the Appendix as described in the SF424 (R&R)
Application Guide.

Foreign Institutions

Foreign (non-US) institutions must follow policies described
in the NIH
Grants Policy Statement, and procedures for foreign institutions described
throughout the SF424 (R&R) Application Guide.

3. Submission Dates and
Times

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in
advance of the deadline to ensure they have time to make any application
corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants
across all Federal agencies. Applicants must then complete the submission
process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

Applicants
are responsible for viewing their application in the eRA Commons to ensure accurate
and successful submission.

Information on the submission process and a definition of
on-time submission are provided in the SF424 (R&R) Application Guide.

For assistance with your electronic application or for more information on the electronic submission
process, visit Applying
Electronically.

Important
reminders:All PD(s)/PI(s) must include their eRA Commons ID in the
Credential fieldof the Senior/Key Person Profile Component of the SF
424(R&R) Application Package. Failure to register in the Commons and
to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent
the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the
application is the same number used in the organization’s profile in the eRA
Commons and for the Central Contractor Registration (CCR). Additional
information may be found in the SF424 (R&R) Application Guide.

Upon receipt, applications will be evaluated for completeness
by the Center for Scientific Review and responsiveness by components of participating organizations,
NIH. Applications that are incomplete and/or nonresponsive will not be
reviewed.

The IBDGC will consist of up to
six GRCs and one Data Coordinating Center (DCC). The DCC is fully described in
the accompanying RFA
DK-11-502. A GRC is an institution that is actively involved in the
recruitment and evaluation of patients, family members and control subjects and
the initiation of individual, center-specific genetic studies taking advantage
of special patient populations. A GRC should consist of an interdisciplinary
team of investigators (e.g.,
research gastroenterologists, human geneticists, immunologists,
microbiologists, as appropriate) and additional necessary personnel, such as a
research coordinator and clerical staff.

GRCs must work in concert with the DCC to implement
procedures for uniform data collection, handling and transmittal of data, as
well as data audits and other data quality control procedures, as established
by the study protocol. GRCs will be required to share data and patient
specimens with other centers in the IBDGC. It is anticipated that the GRCs
will conduct independent analyses (enlisting support from the DCC, as
appropriate), in addition to participating in collaborative projects with other
centers in the IBDGC. The GRCs and DCC will independently and collectively
allocate resources and personnel for the performance of independent,
center-specific, as well as collaborative analyses and studies. GRC members
will staff the various operational committees of the IBDGC (e.g., Recruitment,
Phenotyping, Analytic, etc.), thereby collaborating on the design of joint
projects and establishment of uniform procedures and policies.

There should be evidence of strong institutional support for
the GRC, including adequate space in which to conduct clinical and research
activities and office space for staff. The PD(s)/PI(s) will be expected to
participate in a per patient basis for operational costs of patient specimen
acquisition and processing. A GRC must have the ability to interact with the
DCC and transmit and edit data. GRC members will be required to participate in
the Consortium concept outlined in this solicitation, follow commonly agreed
upon protocols, participate in the Steering Committee meetings and abide by its
decisions.

PD(s)/PI(s) of the GRCs, along with other key personnel,
should plan to attend a one-day organizational meeting of the IBDGC in the
Washington, DC area within 4 months of the award date, and should budget
accordingly.

Beginning in the second award year, the IBDGC Principal
Investigators shall attend a meeting to report on the IBDGC's progress and
plans to an External Advisory Committee (EAC) convened by NIDDK. The EAC shall
include experts in various disciplines related to IBD research (e.g., clinical
gastroenterology, genetics and genomics, mucosal immunology, microbiology), who
will advise NIDDK and the IBDGC about future research directions for the IBDGC,
and opportunities for collaborating with the broader IBD research community.
NIDDK will convene similar meetings of the IBDGC and the EAC at approximately
annual intervals.

Post Submission Materials

Applicants are required to follow the instructions for
post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1.
Criteria

Only the review criteria described below will be considered
in the review process. As part of the NIH mission,
all applications submitted to the NIH in support of biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall Impact

Reviewers will provide an overall impact/priority score to
reflect their assessment of the likelihood for the project to exert a
sustained, powerful influence on the research field(s) involved, in
consideration of the following review criteria and additional review criteria (as
applicable for the project proposed).

Scored Review Criteria

Reviewers will consider each of the review criteria below in
the determination of scientific merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature is not
innovative may be essential to advance a field.

Significance

Does the project address an important problem or a
critical barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change the
concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other
researchers well suited to the project? If Early Stage Investigators or New
Investigators, or in the early stages of independent careers, do they have
appropriate experience and training? If established, have they demonstrated an
ongoing record of accomplishments that have advanced their field(s)? If the
project is collaborative or multi-PD(s)/PI(s), do the investigators have
complementary and integrated expertise; are their leadership approach,
governance and organizational structure appropriate for the project? Do the PD(s)/PI(s) show evidence of previous research productivity in the setting of a research
consortium?

Innovation

Does the application challenge and seek to shift
current research or clinical practice paradigms by utilizing novel theoretical
concepts, approaches or methodologies, instrumentation, or interventions? Are
the concepts, approaches or methodologies, instrumentation, or interventions
novel to one field of research or novel in a broad sense? Is a refinement,
improvement, or new application of theoretical concepts, approaches or
methodologies, instrumentation, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of the project?
Are potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development, will the strategy
establish feasibility and will particularly risky aspects be managed?

If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed? Is the plan for subject recruitment (including numbers of subjects) clearly described? Is there
evidence that the investigators can execute the plan for recruitment?

Environment

Will the scientific environment in which the work
will be done contribute to the probability of success? Are the institutional
support, equipment and other physical resources available to the investigators
adequate for the project proposed? Will the project benefit from unique
features of the scientific environment, subject populations, or collaborative
arrangements? Does the research environment enhance the ability of the
investigators to collaborate with the other GRCs and the DCC?

Additional Review Criteria

As applicable for the project proposed, reviewers will
evaluate the following additional items while determining scientific and
technical merit, and in providing an overall impact/priority score, but will
not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does
not involve one of the six categories of research that are exempt under 45 CFR
Part 46, the committee will evaluate the justification for involvement of human
subjects and the proposed protections from research risk relating to their
participation according to the following five review criteria: 1) risk to
subjects, 2) adequacy of protection against risks, 3) potential benefits to the
subjects and others, 4) importance of the knowledge to be gained, and 5) data
and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or
more of the six categories of research that are exempt under 45 CFR Part 46,
the committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials. For
additional information on review of the Human Subjects section, please refer to
the Human
Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and
Children

When the proposed project involves clinical research,
the committee will evaluate the proposed plans for inclusion of minorities and
members of both genders, as well as the inclusion of children. For additional
information on review of the Inclusion section, please refer to the Human
Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live
vertebrate animals as part of the scientific assessment according to the
following five points: 1) proposed use of the animals, and species, strains,
ages, sex, and numbers to be used; 2) justifications for the use of animals and
for the appropriateness of the species and numbers proposed; 3) adequacy of
veterinary care; 4) procedures for limiting discomfort, distress, pain and
injury to that which is unavoidable in the conduct of scientifically sound
research including the use of analgesic, anesthetic, and tranquilizing drugs
and/or comfortable restraining devices; and 5) methods of euthanasia and reason
for selection if not consistent with the AVMA Guidelines on Euthanasia. For
additional information on review of the Vertebrate Animals section, please
refer to the Worksheet
for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures
proposed are potentially hazardous to research personnel and/or the
environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable.

Renewals

For Renewals, the committee will consider the
progress made in the last funding period.

Revisions

Not Applicable.

Additional Review Considerations

As applicable for the project proposed, reviewers will
consider each of the following items, but will not give scores for these items,
and should not consider them in providing an overall impact/priority score.

Applications from Foreign
Organizations

Reviewers will assess whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions that exist
in other countries and either are not readily available in the United States or
augment existing U.S. resources.

Select Agent Research

Reviewers will assess the information provided in
this section of the application, including 1) the Select Agent(s) to be used in
the proposed research, 2) the registration status of all entities where Select
Agent(s) will be used, 3) the procedures that will be used to monitor
possession use and transfer of Select Agent(s), and 4) plans for appropriate
biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will consider whether the budget and the
requested period of support are fully justified and reasonable in relation to
the proposed research.

2. Review and Selection
Process

Applications will be evaluated for scientific and technical
merit by (an) appropriate Scientific Review Group(s) convened by the NIDDK, in accordance with NIH peer
review policy and procedures, using the stated review
criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

May undergo a selection process in which only those applications
deemed to have the highest scientific and technical merit (generally the top
half of applications under review) will be discussed and assigned an overall impact/priority
score.

Applications will compete for available funds with all other
recommended applications submitted in response to this FOA. Following initial
peer review, recommended applications will receive a second level of review by
the National Diabetes and Digestive and Kidney Disease Advisory Council. The following will be considered in making funding decisions:

Scientific and technical merit of the proposed project as
determined by scientific peer review.

Availability of funds.

Relevance of the proposed project to program priorities.

3. Anticipated Announcement
and Award Dates

After the peer review of the application is completed, the
PD(s)/PI(s) will be able to access his or her Summary Statement (written
critique) via the eRA Commons.

If the application is under consideration for funding, NIH
will request "just-in-time" information from the applicant as
described in the NIH
Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided
to the applicant organization for successful applications. The NoA signed by
the grants management officer is the authorizing document and will be sent via
email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award costs.

The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is
applicable when State and local Governments are eligible to apply), and other
HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this
program will be the cooperative agreement, an "assistance" mechanism
(rather than an "acquisition" mechanism), in which substantial NIH
programmatic involvement with the awardees is anticipated during the
performance of the activities. Under the cooperative agreement, the NIH purpose
is to support and stimulate the recipients' activities by involvement in and
otherwise working jointly with the award recipients in a partnership role; it
is not to assume direction, prime responsibility, or a dominant role in the
activities. Consistent with this concept, the dominant role and prime
responsibility resides with the awardees for the project as a whole, although
specific tasks and activities may be shared among the awardees and the NIH as
defined below.

The PD(s)/PI(s) will have the primary responsibility for:

1. Developing the research design and study protocol,
including definition of objectives and approaches, sample size and power
calculations, and establishing procedures for participant recruitment and follow-up,
data collection, quality control, interim data and safety monitoring, final
data analysis and interpretation, and publication of results.

2. Establishing a Steering Committee to implement,
coordinate and manage the project(s). Awardee(s) will name investigators to
serve as members on a Steering Committee and other subcommittees, as
appropriate, meeting periodically. Awardees will be required to accept and
implement the common protocol(s) and procedures approved by the Steering
Committee.

3. Implementing collection of data specified by the study
protocol, by the Steering Committee. For a multi-center study, each
awardee/site is required to ensure that data will be submitted expeditiously to
the Data Coordinating Center. Additionally, individual investigators/sites must
demonstrate the ability to implement the strategy specifically designed for
their individual study population.

4. Establishing procedures for data quality and
completeness. Awardees are responsible for ensuring accurate and timely assessment
of the progress of each study, including development of procedures to ensure
that data collection and management are: (1) adequate for quality control and
analysis; (2) for clinical trials, as simple as appropriate in order to
facilitate cooperation/referral of study participants by physicians to avoid
unnecessary expense; and (3) sufficiently staffed across the participating
institutions. For research involving multiple awards, a plan for analysis of
pooled data will be developed by the Steering Committee.

5. Submitting interim progress reports, when requested, to
the NIDDK Program Official including as a minimum, summary data on protocol
performance. For coordinated multiple awards or a multi-site single award, the
NIDDK Program Official may require additional information from individual
awardees/sites. Such reports are in addition to the required annual
noncompeting continuation progress report.

6. Establishing procedures, where applicable, for all
participating institutions in coordinated awards to comply with the
requirements of 45 CFR Part 46 for the protection of human subjects, and the
NIH policy requirements for the inclusion of women, minorities and children.

7. Reporting of the study findings. The awardee(s) will
retain custody of and have primary rights to the data developed under these
awards, subject to the Government rights of access consistent with current HHS,
PHS and NIH policies. The awardee must also be adherent to Study Publication
and Presentation Policy. The NIDDK will have access to and may periodically
review all data generated under an award. NIDDK staff may co-author
publications of findings with awardees consistent with NIH and study policies.

8. Support or other involvement of industry or any other
third party in the study -- e.g., participation by the third party; involvement
of study resources or citing the name of the study or NIDDK support; or special
access to study results, primary data/summary information, or resources -- may
be advantageous and appropriate. However, except for licensing of patents or
copyrights, support or involvement of any third party is permitted only after
concurrence by NIDDK.

9. Study investigators are encouraged to publish and to
release publicly and disseminate results and other products of the study, in
accordance with study protocols and steering committee policies on
publications.

10. Maintaining confidentiality of information: The
awardee(s) will maintain the confidentiality of the information developed by
the investigators (i.e., protocols, data analysis, conclusions, etc.) as well
as proprietary information of a company collaborating with the study.

11. The NIDDK has established Central Biosample, Genetic,
and Data Repositories for the

archiving and storage of data and biosamples collected in
large, multi-site studies funded by NIDDK. The PD(s)/PI(s) or his/her designee
will coordinate with the NIDDK Data Repository to prepare the collected data
for eventual archiving and distribution. In addition, if applicable, the PD(s)/PI(s)
or his/her designee will work with the NIDDK Biosample Repository to coordinate
procedures for coding, shipping, processing, receipt, and storage of study
samples that are to be maintained in the Repository. All samples and data
transferred to the Repositories will be under the custodianship of the NIDDK,
although the study’s Steering Committee will have proprietary control of and
exclusive access to the samples and data for an agreed-upon period of time.
Subsequently samples and data will be available to the wider scientific
community in accordance with the NIH policy on Data Sharing (http://grants.nih.gov/grants/policy/data_sharing/ and, http://grants.nih.gov/grants/policy/data_sharing/data_sharing_guidance.htm#goals,
and http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm)

12. The Food and Drug Administration Amendments Act of 2007
(FDAAA or US Public Law 110-85) was passed on September 27, 2007. The law
requires mandatory registration and results reporting for certain clinical
trials of drugs, biologics, and devices. If applicable, the PD(s)/PI(s) or
his/her designee will perform the mandatory study registration and reporting of
study results to ClinicalTrials.gov. For more information about this law and
requirements for sponsors and/or investigators, visit the PRS and U.S. U.S.
Public Law 110-85 Information Page at PRS Information: U.S.
Public Law 110-85.

Awardees will retain custody of and have primary rights to
the data and software developed under these awards, subject to Government
rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that
is above and beyond the normal stewardship role in awards, as described below:

1. Serve as the contact point for all facets of the
scientific interaction with the awardee (s). As required for the coordination of
activities and to expedite progress, NIDDK may designate additional NIDDK staff
to provide advice to the awardee on specific scientific and/or analytic issues.
Such staff may include another Project Scientist or Analyst, who will provide
direct technical assistance to the awardees to optimize the conduct and/or
analysis of the study; or who may assist in the coordination of activities
across multiple sites.

2. For multi-center studies, participation in the Steering
Committee that oversees study conduct. The NIDDK Project Scientist or designee
will be a full participant and voting member of the Steering Committee and, if
applicable, subcommittees.

3. Serving as a resource to study investigators with respect
to other ongoing NIDDK activities that may be relevant to the study to
facilitate compatibility with the NIDDK missions and avoid unnecessary
duplication of effort.

4. Substantial involvement assisting in the design and
coordination of research activities for awardees as elaborated below:

a. Assisting by providing advice in the management and
technical performance of the investigations, coordinating required regulatory
clearances for investigational agents used in the study, which are held by
NIDDK. The NIDDK may reserve the right to cross file or independently file an
Investigational New Drug Application or an Investigational Device Exemption
form with the FDA.

b. The NIDDK Project Scientist or designee may coordinate
activities among awardees by assisting in the design, development, and
coordination of a common research or clinical protocol and statistical
evaluations of data; in the preparation of questionnaires and other data
recording forms; and in the publication of results.

d. The NIDDK Project Scientist or designee may be co-authors
on study publications. In general, to warrant co-authorship, NIDDK staff must
have contributed to the following areas: (a) design of the concepts or
experiments being tested; (b) performance of significant portions of the
activity; (c) participate in analysis and interpretation of study results and
(d) preparation and authorship of pertinent manuscripts.

In addition, a separate NIDDK Program Official identified in
the Notice of Award (NoA) will be responsible for the normal stewardship and
monitoring of the award including review and approval of all progress reports
and all budgetary decisions. Additional responsibilities include:

1. Interacting with the principal investigator(s) on a
regular basis to monitor study progress. Monitoring may include: regular
communications with the PD(s)/PI(s) and staff, periodic site visits,
observation of field data collection and management techniques, quality
control, fiscal review, and other relevant matters; as well as attendance at
Steering Committee, data safety and monitoring board, and related meetings. The
NIDDK retains, as an option, periodic review of progress by researchers not
involved with the study.

2. Reviewing and approving protocols prior to implementation
to insure they are within the scope of peer review, for safety considerations,
as required by Federal regulations.

3. The NIDDK Program Official will monitor protocol
progress, and may request that a protocol study be closed to accrual for
reasons including: (a) accrual rate insufficient to complete study in a timely
fashion; (b) accrual goals met early; (c) poor protocol performance; (d)
patient safety and regulatory concerns; (e) study results that are already
conclusive; and (f) emergence of new information that diminishes the scientific
importance of the study question. The NIDDK will not permit further
expenditures of NIDDK funds for a study after requesting closure except as
specifically approved by the NIDDK.

4. Making recommendations for continued funding based on: a)
overall study progress, including sufficient patient and/or data accrual; b)
cooperation in carrying out the research (e.g., attendance at Steering
Committee meetings, implementation of group decisions, compliance with the
terms of award and reporting requirements); and/or c) maintenance of a high
quality of research, which will allow pooling of data and comparisons across
multiple cooperative agreement awards for common data elements.

5. Appointment of a Data and Safety Monitoring Board (DSMB)
as appropriate; the NIDDK Program Official or their designee will serve as the
Executive Secretary and/or NIDDK program representative on the DSMB.

Areas of Joint Responsibility include:

1. Steering Committee.

A Steering Committee organized by the study investigator(s)
will be the main governing body of the study. The Steering Committee has
primary responsibility to design research activities, establish priorities,
develop common protocols and manuals, questionnaires and other data recording
forms, establish and maintain quality control among awardees, review progress,
monitor patient accrual, coordinate and standardize data management, and cooperate
on the publication of results. Major scientific decisions regarding the core
data will be determined by the Steering Committee. The Steering Committee will
document progress in written reports to the NIDDK Program Official, and will
provide periodic supplementary reports upon request.

The Steering Committee will be composed of all PD(s)/PI(s), (including
those of data coordinating /statistical centers, if any) and co-investigators
as deemed necessary, and the NIDDK Project Scientist. The final structure of
the Steering Committee and voting procedures will be established at the first
meeting. The NIDDK Project Scientist will have voting membership on the
Steering Committee, and as appropriate, its subcommittees. The frequency of
Steering Committee meetings will be dictated by a vote of the members of the
Steering Committee.

A Chairperson of the Steering Committee, other than the
NIDDK Project Scientist, will be selected by the NIDDK. The Chairperson
provides leadership to the Committee by conducting the Steering Committee
meetings, representing the study group to the External Oversight Committee
established by the NIDDK (see item D2 below) and by interacting closely with
the awardees during protocol development and implementation.

2. External Study Oversight.

An independent Data and Safety Monitoring Board will be established
by the NIDDK for Phase III clinical trials or other high risk studies as
appropriate. The Data and Safety Monitoring Board will review interim results
periodically and provide guidance to the NIDDK.

Dispute Resolution:

Any disagreements that may arise in scientific or
programmatic matters (within the scope of the award) between award recipients
and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel
composed of three members will be convened. It will have three members: a designee
of the Steering Committee chosen without NIH staff voting, one NIH designee,
and a third designee with expertise in the relevant area who is chosen by the
other two; in the case of individual disagreement, the first member may be
chosen by the individual awardee. This special dispute resolution procedure
does not alter the awardee's right to appeal an adverse action that is
otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart
D and DHHS regulation 45 CFR Part 16.

A final progress report, invention
statement, and the expenditure data portion of the Federal Financial Report are
required for closeout of an award, as described in the NIH
Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of
2006 (Transparency Act), includes a requirement for awardees of Federal grants
to report information about first-tier subawards and executive compensation
under Federal assistance awards issued in FY2011 or later. All awardees of
applicable NIH grants and cooperative agreements are required to report to
the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants
Policy Statement for additional information on this reporting
requirement.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and
under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.